This study is being conducted to compare the relationship of patient response to treatment to changes in tumor environment.

Key Inclusion Criteria:

• Histologically confirmed diagnosis of stage III (unresectable) or stage IV cutaneous melanoma (non-acral lentiginous) with at least 1 lesion that is measurable by RECIST 1.1 criteria and accessible for biopsies
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Adequate hepatic function
• Adequate renal function
• Adequate bone marrow function
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Able to understand and complete study-related questionnaires
• Anticipated life expectancy >12 weeks

Key Exclusion Criteria:

• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs).
• Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway)
• Prior treatment with other immune modulating anti-cancer agents, except for remote treatment (>6 months) in adjuvant setting.
• Untreated or active brain metastases or spinal cord compression
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of REGN2810

Other protocol-defined inclusion/exclusion criteria will apply